中国科学院大连化学物理研究所机构知识库
Advanced  
DICP OpenIR  > 中国科学院大连化学物理研究所  > 会议论文
学科主题: 物理化学
题名: High-selective hepatic removel of deoxyschizandrin in microsomes in vitro and correlation with perfusion data
作者: Wu JJ(吴敬敬)
会议名称: The 18th Microsomes and Drug Oxidation (MDO) Meeting
会议日期: 2010-5-16
出版日期: 2010-05-16
会议地点: 中国
通讯作者: Ling Yang
部门归属: 十八室
主办者: 中国医学科学院药物研究所
摘要: Aim to develop deoxyschizandrin (DS), one of the major active lignans isolated from Schisandra fruits, as a novel high-selective in vivo CYP3A probe. We investigated the respective contributions of enzyme and transporter to hepatic clearance in vitro and ex vivo. Metabolic stability experiments were conducted with liver microsomes. Then, we determined the disposition of deoxyschizandrin in recirculated perfused rat livers. DS was introduced as a bolus into the perfusate reservoir with or without CYP3A reversible inhibitor ketoconazole (KCZ) and irreversible inhibitor troleandomycin (TAO), and the perfusate, bile and liver samples were collected over 60 min. The hepatic distribution, biliary excretion, and mass balance of DS and its metabolite were investigated. In vitro studies indicated that DS was selectively metabolized by CYP3A4 to schizandrin (SZ) with human liver microsome (HLMs). Identical metabolites profiles were observed in rat liver microsome (RLMs). Both DS and its C-7 hydroxylation metabolite SZ were identified in the perfusate, bile and liver. The levels of formation of other metabolites except for SZ were negligible during our experimental procedure. DS exhibited minimal biliary excretion, representing around 0.001% of the dose administered. The perfusate area under the curve (AUC) of DS was markedly increased in the presence of CYP3A inhibitors; The DS clearance predicted from 7-OH DS data, scaled for total liver mass, was comparable with the hepatic clearance observed ex vivo (5.36±0.19 versus 5.57±0.25 ml/min). In conclusions, hepatic metabolism of DS via CYP3A to SZ is the major hepatic elimination pathway for DS, which improve the probability that DS might be served as a probe drug to evaluate the activity of CYP3A in vivo, providing the opportunity for more personalized medicine.
语种: 中文
内容类型: 会议论文
URI标识: http://cas-ir.dicp.ac.cn/handle/321008/114052
Appears in Collections:中国科学院大连化学物理研究所_会议论文

Files in This Item:

There are no files associated with this item.


Recommended Citation:
Wu JJ. High-selective hepatic removel of deoxyschizandrin in microsomes in vitro and correlation with perfusion data[C]. 见:The 18th Microsomes and Drug Oxidation (MDO) Meeting. 中国. 2010-5-16.
Service
 Recommend this item
 Sava as my favorate item
 Show this item's statistics
 Export Endnote File
Google Scholar
 Similar articles in Google Scholar
 [吴敬敬]'s Articles
CSDL cross search
 Similar articles in CSDL Cross Search
 [吴敬敬]‘s Articles
Related Copyright Policies
Null
Social Bookmarking
  Add to CiteULike  Add to Connotea  Add to Del.icio.us  Add to Digg  Add to Reddit 
所有评论 (0)
暂无评论
 
评注功能仅针对注册用户开放,请您登录
您对该条目有什么异议,请填写以下表单,管理员会尽快联系您。
内 容:
Email:  *
单位:
验证码:   刷新
您在IR的使用过程中有什么好的想法或者建议可以反馈给我们。
标 题:
 *
内 容:
Email:  *
验证码:   刷新

Items in IR are protected by copyright, with all rights reserved, unless otherwise indicated.

 

 

Valid XHTML 1.0!
Powered by CSpace